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Biomedical subjects

F Carnot

Publications and source records attributed to F Carnot.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells.

Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) gene was identified because of its increased expression in 25% of human hepatocellular carcinoma. HIP/PAP protein, a C-type lectin, binds laminin, acts as an adhesion molecule for hepatocytes, and has also been described as an acute phase secretory protein during acute pancreatitis in humans and rats. We investigated HIP/PAP protein expression in patients with various liver diseases associated with ductular reaction. At the same time, we analyzed patients with hepatocellular carcinoma and cholangiocarcinoma, and tested HIP/PAP protein levels in sera to establish the pattern of secretion. Our data show that HIP/PAP expression was not restricted to hepatocellular carcinoma, but was also detected in cholangiocarcinoma cells as well as in reactive non-malignant bile ductules. In contrast, HIP/PAP protein expression was undetectable in normal mature hepatocytes, but some ductular cells localized at the interface of portal tracts with parenchyma were HIP/PAP immunoreactive in normal liver. Finally, we present evidence that HIP/PAP serum levels were increased in 21/28 (75%) patients with hepatocellular carcinoma, and in 25/51 (49%) patients with nonmalignant cirrhosis. Altogether, these results suggest that HIP/PAP protein may be implicated in hepatocytic and cholangiolar differentiation and proliferation.

Acute-Phase Proteins↗
PubMed1998

Predictive factors for development of cirrhosis in parenterally acquired chronic hepatitis C: a comparison between immunocompetent and immunocompromised patients.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact of the host immune status and of virological and environmental parameters on the development of cirrhosis during chronic hepatitis C virus infection. METHODS: Liver histology (cirrhosis or not, Knodell score) was evaluated according to age, sex, route and age of contamination, alcohol consumption and immune status in a large series of 553 HBsAg-negative patients (whose duration of hepatitis C virus infection could be precisely evaluated) divided into three groups: group 1 consisted of 462 immunocompetent subjects (46.1% intravenous drug users, 53.9% transfused), infected for a mean of 12.5+/-6.7 years, including 16.6% of alcohol abusers (>80 g/day); groups 2a and 2b consisted of 91 immunocompromised patients, 52 human immunodeficiency virus-coinfected patients corresponding to group 2a and 39 kidney recipients undergoing immunosuppressive therapy for group 2b, having been infected by hepatitis C virus for a mean of 12.6+/-5.3 and 11.5+/-5.3 years, respectively. RESULTS: Group 1: cirrhosis was present in 11.0% of group 1 patients and in 23.6% of immunocompetent patients with a duration of hepatitis C virus infection of 20 years or more. Forty-three percent of patients with cirrhosis and with hepatitis C virus infection for more than 20 years were alcohol abusers. The time taken to develop cirrhosis was 14+/-7 years in patients infected before the age of 40 years as compared to 8+/-5 years in those infected after 40 years (p<0.001). Groups 2a and 2b: cirrhosis was present in 19.8% of immunocompromised patients, a significantly higher rate than in immunocompetent patients (p<0.01). Alcohol abuse did not increase the risk of cirrhosis in this group. All patients but one were infected by hepatitis C virus before the age of 40 and the calculated time elapsed until the occurrence of cirrhosis was 12.4+/-5.5 years. In groups 1, 2a and 2b, there was no relation between histological severity, hepatitis C virus genotype and viral load. Four variables were independently associated with the occurrence of cirrhosis in the multivariate analysis: age over 40 at time of contamination (RR=9.3 in age range 40 to 59 and 91.2 in > or =60 years); long duration (> or =20 years) of hepatitis C virus infection (RR=15.4); alcohol consumption over 80 g/d (RR=2.9); and human immunodeficiency virus-coinfection (RR=2.6). CONCLUSIONS: Our study on a large series of well-characterized patients provides an accurate evaluation of the risk of cirrhosis in parenterally-contaminated immunocompetent hepatitis C virus-infected patients, with an overall figure of 11%. It also demonstrates the impact of the host immune status on the risk of severe histological lesions during chronic hepatitis C virus infection. It finally establishes the importance of age at the time of viral infection in the occurrence of cirrhosis, as well as the importance of alcohol consumption. Thus, at least following parenteral infection, both host-related and environmental cofactors play a major role in the severity of the liver lesions associated with hepatitis C virus infection.

Adult↗
PubMed1998

Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users.

BACKGROUND/AIM: This retrospective study aimed to better define the respective biological and pathological impact of human immunodeficiency virus infection and chronic alcohol consumption on the course of hepatitis C virus infection in intravenous drug users. METHODS: Two hundred and ten consecutive anti-HCV positive intravenous drug users, among whom 60 were also anti-HIV positive, took part in the study at the University Hospital, Paris, France. RESULTS: The activity of aspartate aminotransferase and gamma-glutamyl transpeptidase was significantly increased in serum from anti-HIV positive patients. The mean hepatitis activity index was significantly higher in anti-HIV positive patients (p<0.05), among whom there was also a higher proportion of patients with cirrhosis as compared to anti-HIV negative patients (30.0 vs 15.3%, p<0.0001). Excessive alcohol drinking (recorded in around 35% of the patients, whatever their HIV status), as compared to non-excessive drinking, was more often associated with cirrhosis in anti-HIV negative (24.5 vs 11.3%, p<0.05) than in anti-HIV positive patients (30.4 vs 29.7%, not significant). In a multivariate analysis, HIV infection (relative risk 2.2, confidence interval 1.1-4.5) and excessive alcohol drinking (relative risk 1.9, confidence interval 1.0-3.9) were the variables independently associated with the risk of cirrhosis. CONCLUSION: Human immunodeficiency virus infection worsens the course of chronic hepatitis C in intravenous drug users. Excessive alcohol drinking also appears to be a crucial negative cofactor, and therefore alcohol withdrawal should be proposed as an integral part of the therapy.

Adult↗
PubMed1998

Hepatitis G virus infection in hepatitis C virus-positive patients co-infected or not with hepatitis B virus and/or human immunodeficiency virus.

This was a retrospective study to evaluate the prevalence and impact of hepatitis G virus (HGV) infection in hepatitis C virus (HCV)-positive drug addicts, according to the serological status of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. Two hundred and thirty-five randomly selected intravenous drug addicted patients (147 French, 88 Italian) were studied. All patients were positive for antibodies to HCV (anti-HCV). HGV RNA positivity was measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Comparisons of HCV RNA positivity rate, and biological and histopathological variables, were made between HGV RNA-positive and negative patients, according to their HBV and HIV status. HGV prevalence was around 30% in both French and Italian groups. No clear association between HGV infection and a particular HCV genotype was observed. The rate of HCV RNA positivity did not differ between HGV-positive and HGV-negative patients after stratification for hepatitis B surface antigen (HBsAg) and HIV positivity. Histological severity of the underlying chronic hepatitis did not differ according to the HGV status; however, in HIV-positive HBsAg-negative patients, the hepatitis activity was moderately increased in HGV-positive patients. A striking negative influence of HBsAg positivity on HCV replication was observed in HIV-negative patients; an HCV RNA-positive rate of 25% was found in HBsAg-positive patients vs 86% in HBsAg-negative patients; similar significant results were observed in HIV-positive patients, although to a lesser extent. The underlying chronic hepatitis was significantly more severe in HBsAg-positive than in HBsAg-negative HIV-negative patients. Hence, HGV infection is highly prevalent in anti-HCV positive drug addicts but the co-infection with HCV does not seem to influence HCV replication nor to worsen the underlying chronic hepatitis, in HIV-negative patients at least. Reciprocal influence between HBV, HCV and HIV appears rather complex, HBsAg carriage seeming to exert per se a negative effect on HCV replication, particularly in HIV-negative patients, suggesting that interactions between hepatitis viruses should always be analysed in the light of HIV status.

Adult↗
PubMed1998

Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy.

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis of human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. The precise impact, if any, of anti-HIV triple therapy on hepatitis C virus (HCV) infection is unknown. We describe an unusual case of rapidly evolving HCV-related cirrhosis that paralleled restoration of immune status in an HIV-infected patient and discuss the possible link between such a severe course of hepatitis C and anti-HIV triple therapy.

Adult↗
PubMed1998

[Severe hemorrhagic gastritis of radiation origin].

Severe gastric complications due to radiotherapy are uncommon, in particular hemorrhagic gastritis. A high total dose and, above all, high daily fraction appear to be the main risk factors in gastric injuries. A case of hemorrhagic gastritis induced by radiotherapy requesting a total gastrectomy is reported. The patient was treated for a primary gastric non-Hodgkin's lymphoma. Hemorrhagic gastritis occurred despite a low total dose (40 Gy) and 2 Gy daily fractions. Upper gastrointestinal endoscopy and repeated biopsies are usually insufficient to exclude a tumor recurrence. Endoscopic ultrasonography may argue for a recurrence or for radiation lesions. As the conservative treatment is usually ineffective, these gastrointestinal radiation injuries ought to be treated surgically. Besides it allows to ascertain the benign nature of radiation lesions.

Gastritis↗
PubMed1997

Hepatitis C virus-related fibrosing cholestatic hepatitis after renal transplantation.

Fibrosing cholestatic hepatitis is a well-described syndrome in patients with immunodeficiency and chronic hepatitis B. It is clinically, biologically, and histologically characterized by rapidly progressive hepatic failure, a mildly elevated serum aminotransferase level, an extensive periportal fibrosis associated with intense cholestasis, mild inflammatory cellular infiltrate, no cirrhosis, and a high hepatocellular level expression of B viral antigens. This syndrome reflected a direct hepatocytopathic injury linked to high intrahepatic viral antigen expression. Because the syndrome of fibrosing cholestatic hepatitis has not been described in chronic hepatitis C, we report the first well-characterized case in a renal transplant patient with chronic hepatitis C and discuss the clinical and pathogenic implications of such a syndrome in this setting.

Adult↗
PubMed1997

Diversion-related experimental colitis in rats.

PURPOSE: Diversion-related colitis is an inflammatory process that affects the colon and/or rectum distal to a colostomy. Its mechanisms are unknown, and many hypotheses have been considered. The aim of the present study was to create an experimental model of diversion-related colitis in rats, so in the future it will be possible to test different hypotheses. METHODS: Three groups of ten male Wistar rats were used for the study. Two groups underwent a colostomy and were kept alive for 6 or 17 weeks. One group of rats was killed at the onset of the experiment. Specimens were taken in bypassed segments in the rats who had had a colostomy and in the sigmoid colon for the control group. Histologic analysis using standard coloration, histochemical techniques, and bacterial preparation was used to find histologic or changes of colonic histology or flora. RESULTS: Exclusion was associated with vascular congestion, a decrease in length of glandular crypts (P < 0.01), and an erosion of surface epithelium; inflammation of the mucosa was absent in all control animals and present in all test animals. In contrast, the number of goblet cells was not changed by the procedure. There was also a significant change in distribution and intensity of sulfomucins and sialomucins and quantitative and qualitative changes of the colonic flora. CONCLUSION: This experimental model of diversion colitis is characterized by histologic and bacteriologic modifications comparable with those reported in humans but with different histochemical changes.

Animals↗
PubMed1997

[Histological aspects of naso-ethmoidal tumors].

Among malignant neoplasms of the sino-nasal tract, tumors of the nasal vault have special features: their higher incidence in woodworkers, their frequent local recurrence and invasiveness in the skull base. Histologically too, they are peculiar by the predominance of the glandular tumors, of colonic or enteric type especially. Microscopic examination allows histological grading of these adenocarcinoma. Squamous carcinoma and adenoid cystic carcinoma are less frequent than in other parts of the sinonasal tract. Rare other tumors, often undifferentiated, can be diagnosed by immuno-staining as esthesioneuroblastomas, malignant melanomas, neuro-endocrine carcinomas, malignant lymphomas or sarcomas. A retrospective study of 147 patients yielded similar data.

Ethmoid Sinus↗
PubMed1996

The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection.

In an attempt to evaluate the long-term reciprocal impact of renal transplantation on hepatitis B virus infection, we analyzed the clinical, virologic, and pathologic features of 151 HBsAg-positive kidney transplant recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%, respectively, figures lower than in the general population. A high rate of persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy was the high frequency of histologic deterioration (85.3%), accompanied by cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated with histologic worsening. Liver disease was the leading cause of death (36.6%), especially in patients with cirrhosis. Despite persistent viral replication, histopathologic deterioration, and liver-related overmortality, there were paradoxically no significant differences in the survival of these 151 HBsAg-positive compared with 1247 HBsAg-negative kidney recipients--however, allograft actuarial survival was better in the former than in the latter group (P=0.0006). Chronic hepatitis B infection is not a contraindication to renal transplantation in the absence of cirrhosis. The presence of cirrhosis should lead either to dialysis continuation or to a combined liver/kidney transplantation, in the absence of viral replication.

Adult↗
PubMed1996

Azathioprine hepatitis in kidney transplant recipients. A predisposing role of chronic viral hepatitis.

Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.

Adult↗
PubMed1996

Effectiveness and tolerance of interferon-alpha 2b in the treatment of chronic hepatitis C in haemodialysis patients.

Twenty-five per cent of haemodialysed patients carry anti-HCV antibodies; these antibodies are associated with detectable viraemia in 85% and chronic hepatitis in 90% of subjects, despite normal transaminases in more than half of them. This underlines the importance of antiviral therapy. We evaluated the tolerance and effectiveness of a classic interferon (IFN) treatment (3 MU three times a week for 6 months, subcutaneously) in 19 haemodialysis patients presenting with anti-HCV antibodies and chronic (n = 16) or acute (n = 3) hepatitis. Thirteen of those 19 patients had elevated transaminases. Viraemia C was detected by genome amplification (PCR) and by the bDNA test before and after interferon therapy as well as 6 months at least after the end of INF treatment. Response (defined as liver enzyme normalization) was noted in 11 (84.6%) of the 13 patients with elevated transaminases; at the end of follow-up, six exhibited long-term response and five had relapsed, HCV-RNA was detected in 15 of the 19 patients before IFN therapy and remained positive in 7/15 initially viraemic patients at the end of treatment. Hepatitis C RNA was detected at the last follow-up visit (mean follow-up duration 18 +/- 9 months) in 12 of the 15 initially viraemic patients. Liver histology was improved in most patients, regardless of their biological response. One patient could not complete the 6-month course because of clinical and haematological adverse events. In the six patients with strictly normal transaminases, HCV RNA was detectable in 4/6 patients before treatment, in 2/4 viraemic patients at the end of treatment, and in 4/4 at the last follow-up visit. All pathological signs disappeared in four of the five patients who had no detectable HCV-RNA before IFN therapy. To conclude: (i) interferon-alpha exhibits satisfactory effectiveness and tolerance in haemodialysed patient; (ii) HCV replication recurs in most of these patients despite histological improvement; (iii) interferon-alpha can be effective even in patients with chronic hepatitis and no detectable HCV-RNA.

Antibodies, Viral↗
PubMed1996

HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells.

Human hepatocarcinoma-intestine-pancreas (HIP) cDNA, isolated from a hepatocellular carcinoma, encodes a C-type lectin. According to published cDNA sequences, HIP protein is identical to human pancreatitis-associated protein (PAP). In these sequences, a putative signal peptide and the carbohydrate recognition domain (CRD) can be recognized. In the present study, we established transgenic mice to drive the production of soluble recombinant HIP/PAP protein in the milk of lactating animals; using this model, we showed that HIP/PAP protein was secreted after suitable cleavage of the potential signal peptide. Moreover, we also produced HIP/PAP protein by Escherichia coli cultures performed to generate specific antibodies. These antibodies enabled the detection of HIP/PAP protein in normal intestine and pancreas (both in endocrine and exocrine cells), e.g., intestinal neuroendocrine and Paneth cells, pancreatic islets of Langerhans, and acinar cells. HIP/PAP protein was also identified in the cytoplasm of tumoral hepatocytes but not in nontumoral hepatocytes. Finally, HIP/PAP protein activity was tested and we showed that HIP/PAP induced the adhesion of rat hepatocytes and bound strongly to extracellular matrix proteins (laminin-1, fibronectin), less strongly to type I and IV collagen, and not at all to heparan sulfate proteoglycan. In conclusion, these results showed that HIP/PAP protein was matured on secretion. We also demonstrated that HIP/PAP protein was specifically expressed in hepatocarcinoma cells and interacted with rat hepatocytes and the extracellular matrix. Taken overall, these results suggest that HIP/PAP protein may be of potential importance to liver cell differentiation/proliferation.

Acute-Phase Proteins↗
PubMed1996

[Primary non-Hodgkin's lymphomas of the liver in human immunodeficiency virus infected patients. Three cases].

The occurrence of primary non Hodgkin's lymphoma of the liver has rarely been reported in patients with the human immunodeficiency virus infection. We report 3 cases in these patients, presenting with a single liver tumor in 2 cases and multiple tumors in one case. Diagnosis was made by guided-biopsy. Histologically, there was B diffuse large cell lymphoma in 2 cases, and immunoblastic lymphoma in one case. In one case, RNA of Epstein-Barr virus was found in the nucleus of tumor cells by in situ hybridization. No extrahepatic localization was found in any of the 3 cases. One patient died one week after diagnosis, but the 2 other patients were treated by chemotherapy and were still alive 6 and 30 months later. In patients infected by human immunodeficiency virus, primary non Hodgkin's lymphoma should be investigated in case of liver tumor in order to provide early treatment.

AIDS-Related Opportunistic Infections↗